Sign up to receive free email alerts when patent applications with chosen keywords are publishedSIGN UP

Abstract:

A passive wireless gastroesophageal sensor includes a LC resonance
circuit, two or more electrodes and a passive batteryless Radio Frequency
Identification (RFID) circuit connected to the LC resonance circuit and
the one or more electrodes. The electrodes are configured to measure an
impedance within a gastroesophageal tract. The passive batteryless RFID
circuit transmits a frequency modulated signal using the LC resonance
circuit that varies between a first frequency corresponding to a non-acid
reflux condition and a second frequency corresponding to an acid reflux
condition based on the measured impedance in response to a signal
received from a detector.

Claims:

1. A passive wireless gastroesophageal sensor comprising:a LC resonance
circuit;two or more electrodes configured to measure an impedance within
a gastroesophageal tract; anda passive batteryless Radio Frequency
Identification (RFID) circuit connected to the LC resonance circuit and
the one or more electrodes to transmit a frequency modulated signal using
the LC resonance circuit that varies between a first frequency
corresponding to a non-acid reflux condition and a second frequency
corresponding to an acid reflux condition based on the measured impedance
in response to a signal received from a detector.

2. The sensor as recited in claim 1, wherein:the non-acid reflux condition
comprises a gas, air, food, drink, saliva or other substance before the
substance has entered a stomach disposed on or between the electrodes;
andthe acid reflux condition comprises a stomach acid or stomach contents
disposed on or between the electrodes.

3. The sensor as recited in claim 1, wherein:the first frequency comprises
a measured frequency of between 6 kHz and 11 kHz; andthe second frequency
comprises a measured frequency greater than 11 kHz.

4. The sensor as recited in claim 1, wherein:the LC resonance circuit
comprises a parallel connected antenna and a capacitor; andthe passive
batteryless RFID circuit comprises a voltage regulator, a voltage
multiplies connected to the voltage regulator, a transistor switch
connected in parallel between the LC resonance circuit and the voltage
multiplier, and an impedance to frequency converter connected the
electrodes and the voltage regulator wherein the impedance to frequency
converter controls the transistor switch.

5. The sensor as recited in claim 1, wherein the LC resonance circuit, the
electrodes and the passive batteryless RFID circuit comprise the circuits
illustrated in FIGS. 5, 6 and 7.

6. The sensor as recited in claim 1, wherein the sensor is configured as a
capsule, a tag or an implant having an overall size equal to or less than
0.5.times.1.times.3 cm.sup.3.

7. The sensor as recited in claim 3, wherein the antenna comprises at
least one wire coil surrounding the electrodes.

8. The sensor as recited in claim 6, wherein the wire coil comprises at
least 15 turns of a conductor having a width of 200 μm and a spacing
of 50-.mu.m in each turn.

9. The sensor as recited in claim 1, wherein the electrodes comprises at
least 10 interdigitated fingers that are about 0.4 mm wide and about 5 mm
long with about 0.1 mm spacing there between.

11. The sensor as recited in claim 1, wherein the electrodes are
fabricated by a process comprising the steps of:evaporating a first
conductive material on a flexible polyimide substrate;patterning a
photoresist layer on selected portions of the first conductive
material;electroplating the first conductive material;removing the
photoresist layer and etching the first conductive material to form the
electrodes;patterning an epoxy based negative resist layer;
andelectroplating a second conductive material on the electrodes.

12. A system for detecting Gastroesophageal Reflux Disease (GERD) in an
animal comprising:a detector comprising:an external resonance circuit
formed from an external coil,a power amplifier connected to the external
resonance circuit,a radio frequency source connected to the power
amplifier,an envelope detector connected to the power amplifer, anda band
pass filter connected to the envelope detector; andone or more passive
wireless gastroesophageal sensors, each sensor comprising:a LC resonance
circuit,two or more electrodes configured to measure an impedance within
a gastroesophageal tract, anda passive batteryless Radio Frequency
Identification (RFID) circuit connected to the LC resonance circuit and
the one or more electrodes to transmit a frequency modulated signal using
the LC resonance circuit that varies between a first frequency
corresponding to a non-acid reflux condition and a second frequency
corresponding to an acid reflux condition based on the measured impedance
in response to a signal received from the detector.

13. The system as recited in claim 12, wherein the power amplifier
comprises the circuit illustrated in FIG. 10 and the envelope detector
comprises the circuit illustrated in FIG. 11.

14. The system as recited in claim 12, wherein:the first frequency
comprises a measured frequency of between 6 kHz and 11 kHz; andthe second
frequency comprises a measured frequency greater than 11 kHz.

15. The system as recited in claim 12, wherein:the LC resonance circuit
comprises a parallel connected antenna and a capacitor; andthe passive
batteryless RFID circuit comprises a voltage regulator, a voltage
multiplies connected to the voltage regulator, a transistor switch
connected in parallel between the LC resonance circuit and the voltage
multiplier, and an impedance to frequency converter connected the
electrodes and the voltage regulator wherein the impedance to frequency
converter controls the transistor switch.

16. The system as recited in claim 12, wherein the one or more sensors
comprise multiple sensors implanted to detect a refluxate in multiple
areas of the gastroesophageal tract of the animal.

17. The system as recited in claim 12, wherein the electrodes are
fabricated by a process comprising the steps of:evaporating a first
conductive material on a flexible polyimide substrate;patterning a
photoresist layer on selected portions of the first conductive
material;electroplating the first conductive material;removing the
photoresist layer and etching the first conductive material to form the
electrodes;patterning an epoxy based negative resist layer;
andelectroplating a second conductive material on the electrodes.

18. The system as recited in claim 12, wherein the external resonance
circuit is uniquely coupled to each sensor.

19. The system as recited in claim 12, wherein the external resonance
circuit is uniquely coupled to more than one of the sensors.

20. The system as recited in claim 12, wherein the sensor comprises
multiple sensors implanted to detect refluxate in multiple areas of the
gastroesophageal system.

21. A method of wirelessly detecting a refluxate in the gastroesophageal
system of an animal comprising the steps of:(a) implanting in the
gastroesophageal system of the animal an untethered sensor comprising:a
LC resonance circuit,two or more electrodes configured to measure an
impedance within the gastroesophageal tract, anda passive batteryless
Radio Frequency Identification (RFID) circuit connected to the LC
resonance circuit and the one or more electrodes to transmit a
frequencymodulated signal using the LC resonance circuit that varies
between a first frequency corresponding to a non-acid reflux condition
and a second frequency corresponding to an acid reflux condition based on
the measured impedance in response to a signal received from a detector
external to the animal;(b) detecting the transmitted frequency using a
detector comprising:an external resonance circuit formed from an external
coil,a power amplifier connected to the external resonance circuit,a
radio frequency source connected to the power amplifier,an envelope
detector connected to the power amplifer, anda band pass filter connected
to the envelope detector; and(c) determining an acidity of the refluxate
based on the detected frequency.

22. The method as recited in claim 21, wherein:the first frequency
comprises a measured frequency of between 6 kHz and 11 kHz; andthe second
frequency comprises a measured frequency greater than 11 kHz.

23. The method as recited in claim 21, wherein:the LC resonance circuit
comprises a parallel connected antenna and a capacitor; andthe passive
batteryless RFID circuit comprises a voltage regulator, a voltage
multiplies connected to the voltage regulator, a transistor switch
connected in parallel between the LC resonance circuit and the voltage
multiplier, and an impedance to frequency converter connected the
electrodes and the voltage regulator wherein the impedance to frequency
converter controls the transistor switch.

Description:

PRIORITY CLAIM TO RELATED APPLICATIONS

[0001]This patent application is a non-provisional application of U.S.
provisional patent application 60/896,912 filed on Mar. 24, 2007 and
entitled "Implantable Wireless RFID Impedance Sensor for Detecting
Gastroesopageal Reflux" which is hereby incorporated by reference in its
entirety.

FIELD OF THE INVENTION

[0002]The present invention relates generally to the field of medical
devices and in particular to improved methods of detecting medical
conditions such as gastroesophageal reflux through wireless systems.

BACKGROUND OF THE INVENTION

[0003]Gastroesophageal reflux disease (GERD) is a medical condition that
affects approximately 15% of adult population in the United States and is
one of the most prevalent clinical conditions afflicting the
gastrointestinal tract. GERD refers to symptoms or tissue damage caused
by the reflux of stomach contents into the esophagus and pharynx. The
most common symptom of GERD is heartburn and acid regurgitation. GERD has
been associated with esophageal cancer and chronic lung damage. Two
common esophageal cancers are squamous cell carcinoma and adenocarcinoma.
In the United States, esophageal carcinoma accounts for 10,000 to 11,000
deaths per year. Adenocarcinoma of esophagus has the fastest growing
incidence rate of all cancers. These increased rates are strongly related
to GERD which is the primary risk factor recognized [1]. Therefore,
monitoring the GERD symptoms comfortably and reliably becomes more
important for early diagnosis of esophageal cancer.

[0004]While pH testing has been used to detect acid reflux, esophageal
impedance monitoring is a new technique that can detect episodes of
gastroesophageal reflux that are both acidic and non-acidic in nature.
This technique overcomes the limit of ambulatory pH-metry which does not
always reliably detect the reflux of material whose pH value is more than
4.0 [2]. Multichannel intraluminal impedance (MII) probe is a currently
available instrument that has been used to correlate symptoms with
episodes of gastroesophageal reflux. Whereas electric conductivity is
directly related to the ionic concentration of the intraluminal content,
materials with high ionic concentrations (e.g. gastric juice or food
residues) have relatively low impedance compared with that of the
esophageal lining or air

[0005]Although the MII probe system brings more accurate monitoring
results compared to the conventional pH meter alone, the configuration is
bulky and uncomfortable for patients. The tethered sensor probe requires
a transnasal insertion procedure and the wire, connecting from the
electrodes that stay inside the esophagus to the external electronic unit
worn by the patient, stays transnasally for 24 to 48 hours while the
patient supposedly resumes normal daily activities. The wired feature
limits the clinical utility and accuracy of this technique for protracted
monitoring of gastroesophageal reflux. A miniature wireless device that
does not require tethered external connections is thus preferred for
esophageal reflux monitoring.

[0006]To date, a wireless pH monitoring capsule (BRAVO, Medtronic) has
been used in some clinical practices [4]. However, it cannot detect
non-acid reflux and has a limited battery life. Recent studies and
reviews have suggested combined pH and impedance monitoring increased the
accuracy of GERD diagnosis [5, 6]. Lately, a combined impedance and pH
sensor capsule that could detect both acid and no-acid reflux was
developed using a microcontroller and a wireless transmitter [7].
However, the device has limited sampling rates to conserve battery
energy. The limited sampling rate may miss reflux episodes between
sampling. The limited battery lifetime prohibits the possibility of
prolonged measurements that in some clinical cases are needed for
increased diagnosis accuracy [8]. Although batteryless wireless
approaches for communication of implantable devices have been proposed
[9, 10], they are not currently utilized for reflux diagnosis using an
impedance to frequency converter.

[0007]Accordingly, there remains a need for an improved system that
accurately monitors a patient's gastroesophageal acid reflux that is more
compact, untethered, improves patient comfort, and does not depend upon
an implanted power source for its function.

SUMMARY OF THE INVENTION

[0008]The present invention provides an improved system that accurately
monitors a patient's gastroesophageal acid reflux that is more compact,
untethered, improves patient comfort, and does not depend upon an
implanted power source for its function. Moreover, the present invention
provides a new method for long term monitoring of gastroesophageal
reflux. Based on inductive coupling, the impedance of the reflux can be
determined remotely without the need of a battery in the implant. The
device includes an energy harvesting circuit, sensing electrodes, an
antenna and an impedance to frequency converter. The external reader
provides power to the implant and measures the impedance values
simultaneously. For example, in one embodiment, a prototype with an
overall size of 0.5×1×3 cm3, was made using a printed
circuit board and discrete components. The device was coated with
polydimethylsiloxane (PDMS) for implant uses. Experiments were conducted
on pig cadavers. The impedance sensor was placed inside the esophagus
along with a commercial wireless pH capsule (BRAVO, Medtronic) to compare
the performance. The results show good correlation between impedance and
pH values of the solutions flushed into the esophagus. Only the impedance
sensor can detect non-acid materials, however. The batteryless wireless
impedance sensor is able to detect every reflux episode, either acid or
non-acid, which will provide more accurate diagnosis of the
gastroesophgeal reflux disease (GERD).

[0009]A first embodiment of the present invention provides a passive
wireless gastroesophageal sensor that includes a LC resonance circuit,
two or more electrodes and a passive batteryless Radio Frequency
Identification (RFID) circuit connected to the LC resonance circuit and
the one or more electrodes. The electrodes are configured to measure an
impedance within a gastroesophageal tract. The passive batteryless RFID
circuit transmits a frequency modulated signal using the LC resonance
circuit that varies between a first frequency corresponding to a non-acid
reflux condition and a second frequency corresponding to an acid reflux
condition based on the measured impedance in response to a signal
received from a detector.

[0010]A second embodiment of the present invention provides a system for
detecting Gastroesophageal Reflux Disease (GERD) in an animal that
includes a detector and one or more sensors. The detector includes an
external resonance circuit formed from an external coil, a power
amplifier connected to the external resonance circuit, a radio frequency
source connected to the power amplifier, an envelope detector connected
to the power amplifier, and a band pass filter connected to the envelope
detector. The sensor includes a LC resonance circuit, two or more
electrodes and a passive batteryless Radio Frequency Identification
(RFID) circuit connected to the LC resonance circuit and the one or more
electrodes. The electrodes are configured to measure an impedance within
a gastroesophageal tract. The passive batteryless RFID circuit transmits
a frequency modulated signal using the LC resonance circuit that varies
between a first frequency corresponding to a non-acid reflux condition
and a second frequency corresponding to an acid reflux condition based on
the measured impedance in response to a signal received from the
detector.

[0011]A third embodiment of the present invention provides a method of
wirelessly detecting a refluxate in the gastroesophageal system of an
animal by implanting in the gastroesophageal system of the animal an
untethered sensor, detecting a transmitted frequency from the sensor
using a detector, and determining an acidity of the refluxate based on
the detected frequency. The detector includes an external resonance
circuit formed from an external coil, a power amplifier connected to the
external resonance circuit, a radio frequency source connected to the
power amplifier, an envelope detector connected to the power amplifier,
and a band pass filter connected to the envelope detector. The sensor
includes a LC resonance circuit, two or more electrodes and a passive
batteryless Radio Frequency Identification (RFID) circuit connected to
the LC resonance circuit and the one or more electrodes. The electrodes
are configured to measure an impedance within a gastroesophageal tract.
The passive batteryless RFID circuit transmits a frequency modulated
signal using the LC resonance circuit that varies between a first
frequency corresponding to a non-acid reflux condition and a second
frequency corresponding to an acid reflux condition based on the measured
impedance in response to a signal received from the detector.

[0012]These embodiments and additional embodiments of the present
invention are described in detail below with reference to the
accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

[0013]The above and further advantages of the invention may be better
understood by referring to the following description in conjunction with
the accompanying drawings, in which:

[0014]FIG. 1 illustrates a wireless impedance sensor system in accordance
with the present invention;

[0015]FIG. 2 is a block diagram illustrating a sensor in accordance with
the present invention;

[0016]FIG. 3A is a schematic diagram illustrating a basic operating
principle of a system in accordance with the present invention;

[0017]FIG. 3B illustrates the frequency modulated signals received at the
reader coil in accordance with the present invention;

[0018]FIG. 4 is a block diagram of a transponder in accordance with one
embodiment of the present invention;

[0019]FIG. 5 is a circuit diagram of a voltage multiplier and voltage
regulator in accordance with one embodiment of the present invention;

[0020]FIG. 6 is a circuit diagram of an impedance-to-frequency converter
and electrodes in accordance with one embodiment of the present
invention;

[0021]FIG. 7 is a circuit diagram of a modulation circuit in accordance
with one embodiment of the present invention;

[0022]FIG. 8 is an image of a batteryless wireless impedance sensor
prototype in accordance with one embodiment of the present invention;

[0023]FIG. 9 is a block diagram of a reader in accordance with one
embodiment of the present invention;

[0024]FIG. 10 is a circuit diagram of a class-E power amplifier in
accordance with one embodiment of the present invention;

[0025]FIG. 11 is a circuit diagram of an envelope detector circuit in
accordance with one embodiment of the present invention;

[0026]FIGS. 12A-12D are graphs of detected signals from the impedance
sensor displayed in a spectrum analyzer in accordance with one embodiment
of the present invention;

[0027]FIG. 13 is a graph illustrating the read frequencies from the
impedance sensor in accordance with one embodiment of the present
invention and the respective pH values from the BRAVO device;

[0028]FIG. 14 is a graph illustrating the measured frequencies from the
impedance sensor in accordance with one embodiment of the present
invention and pH values from the BRAVO device in a pig's esophagus;

[0029]FIG. 15 is a graph illustrating the test results from the impedance
sensor in accordance with one embodiment of the present invention and pH
values from the BRAVO device in another pig cadaver;

[0030]FIGS. 16A, 16B and 16C illustrate various antenna configurations in
accordance with the present invention;

[0031]FIGS. 17A and 17B illustrate various packaging configurations in
accordance with the present invention;

[0032]FIGS. 18A and 18B illustrate various array configurations in
accordance with the present invention;

[0033]FIG. 19 illustrates a system having multiple wireless impedance
sensors in accordance with the present invention;

[0034]FIGS. 20A-20F illustrate a method of fabricating the coil and the
electrodes using a photolithography processes in accordance with the
present invention;

[0035]FIG. 21 shows an electrode having interdigitated fingers in
accordance with one embodiment of the present invention;

[0036]FIG. 22 shows a connector (jumper wire) used to complete the circuit
of the coil and the electrodes in accordance with one embodiment of the
present invention;

[0037]FIG. 23 shows a sensor disposed on a flexible substrate in
accordance with one embodiment of the present invention; and

[0038]FIG. 24 shows a sensor configured for use in a tag in accordance
with one embodiment of the present invention.

DETAILED DESCRIPTION OF THE INVENTION

[0039]While the making and using of various embodiments of the present
invention are discussed in detail below, it should be appreciated that
the present invention provides many applicable inventive concepts that
can be embodied in a wide variety of specific contexts. The specific
embodiments discussed herein are merely illustrative of specific ways to
make and use the invention and do not delimit the scope of the invention.

[0040]The present invention provides an improved system that accurately
monitors a patient's gastroesophageal acid reflux that is more compact,
untethered, improves patient comfort, and does not depend upon an
implanted power source for its function. Moreover, the present invention
provides a new method for long term monitoring of gastroesophageal
reflux. Based on inductive coupling, the impedance of the reflux can be
determined remotely without the need of a battery in the implant. The
device includes an energy harvesting circuit, sensing electrodes, an
antenna and an impedance to frequency converter. The external reader
provides power to the implant and measures the impedance values
simultaneously. For example, in one embodiment, a prototype with an
overall size of 0.5×1×3 cm3, was made using a printed
circuit board and discrete components. The device was coated with
polydimethylsiloxane (PDMS) for implant uses. Experiments were conducted
on pig cadavers. The impedance sensor was placed inside the esophagus
along with a commercial wireless pH capsule (BRAVO, Medtronic) to compare
the performance. The results show good correlation between impedance and
pH values of the solutions flushed into the esophagus. Only the impedance
sensor can detect non-acid materials, however. The batteryless wireless
impedance sensor is able to detect every reflux episode, either acid or
non-acid, which will provide more accurate diagnosis of the
gastroesophgeal reflux disease (GERD).

[0041]Now referring to FIG. 1, a wireless impedance sensor system 100 in
accordance with the present invention is shown. The present invention
uses passive telemetry to wirelessly monitor reflux 102 from an animal's
stomach 104 using a small passive sensor 106 without a battery that can
be attached to the esophagus 108 wall. The implanted sensor 106 harvests
radio frequency (RF) powers 110 transmitted from an external reader or
detector 112 and transduces impedance variations in the esophagus 108 as
RF signals back to the reader 112. As will be further described below, a
prototype of the wireless impedance sensor 106 was made and the device
was tested in pig cadavers to validate the system functionality.

[0042]Referring now to FIG. 2, a block diagram illustrating a sensor 106
in accordance with the present invention is shown. The passive wireless
gastroesophageal sensor 106 includes a LC resonance circuit 200, two or
more impedance measuring electrodes 202 and a passive batteryless Radio
Frequency Identification (RFID) circuit 204 connected to the LC resonance
circuit 200 and the one or more electrodes 202. The electrodes 202 are
configured to measure an impedance within a gastroesophageal tract. The
passive batteryless RFID circuit 204 transmits a frequency modulated
signal using the LC resonance circuit that varies between a first
frequency corresponding to a non-acid reflux condition and a second
frequency corresponding to an acid reflux condition based on the measured
impedance in response to a signal received from a detector. The non-acid
reflux condition may include a gas, air, food, drink, saliva or other
substance before the substance has entered a stomach disposed on or
between the electrodes. The acid reflux condition may include a stomach
acid or stomach contents disposed on or between the electrodes. In one
example and as illustrated by the test results (FIGS. 12A-12D, 13, 14 and
15), the first frequency can be a measured frequency of between 6 kHz and
11 kHz, and the second frequency can be a measured frequency greater than
11 kHz. The sensor 106 can be configured as a capsule, a tag or an
implant.

[0043]Now referring to FIG. 3A, a schematic diagram illustrating a basic
operating principle of a system 300 in accordance with the present
invention is shown. Similar to RFID (radio frequency identification)
techniques [11], the present invention includes a transponder 302 and a
reader 112 in which the communication is based on inductive coupling
between two coils 304 and 306. The reader coil 304 generates
electromagnetic fields coupling into the transponder coil 306. Each coil
304 and 306 is connected to a capacitor 308 and 310, respectively,
forming resonance at the same frequency. In the near field region, the
impedance seen by the reader coil 304 changes when the switch 312 at the
transponder 302 opens or closes. This load modulation alters the voltage
level at the reader coil 304. The variable-frequency source 314 connected
to the reader 112 adjusts to the resonant frequency resulting in high
amplitude signals at the reader coil 304. The variable frequency is
usually much higher than that of the modulating frequency at the
transponder 302.

[0044]Referring now to FIG. 3B, the frequency modulated signals 350
received at the reader coil 304 in accordance with the present invention
are shown. When the switch 312 at the transponder 302 is open (OFF 352),
the signal amplitude at the reader 112 is large due to the low loading
effect. When the switch 312 is close (ON 354), the transponder 302 loads
the reader coil 304 and the reader 112 shifts away from the resonance
condition. Thus the signal amplitude is reduced. The switching frequency
at the transponder 302 varies with the sensing electrode impedance. When
the impedance of refluxant material on the electrode is high, the switch
312 is modulated with a low frequency 356. When the impedance of
refluxant material on the electrode is low, the switch 312 is modulated
with a high frequency 358. As a result, the transponder 302 switching
frequency indicates the measured impedance and can be extracted at the
reader 112 using envelope detection. Therefore, a batteryless wireless
impedance sensor is achieved.

[0045]Now referring to FIG. 4, a block diagram of a transponder (sensor)
106 in accordance with one embodiment of the present invention is shown
[12]. The front end is a parallel connected antenna 306 and a capacitor
310 forming a LC resonance circuit 200 to receive RF powers from the
reader 112. The passive batteryless RFID circuit 204 includes a voltage
multiplier 400, a voltage regulator 402, an impedance to frequency
converter 404 and a transistor switch 312. The voltage multiplier 400 is
connected to the voltage regulator 402. The transistor switch 312 is
connected in parallel between the LC resonance circuit 200 and the
voltage multiplier 400. The impedance to frequency converter 404 is
connected the electrodes 202 and the voltage regulator 402. The impedance
to frequency converter 404 controls the transistor switch 312. The
voltage multiplier 400 consists of a series of diodes and capacitors
(FIG. 5), and increases received RF signals from hundreds of millivolts
to volts. The voltage regulator 402 keeps the DC level constant for
biasing the circuits. The impedance to frequency converter 404 converts
the impedance of electrode 202 to frequency-varying signals. An
interdigitated electrode 202 is selected because of its sensitivity to
impedance changes. In one example, the electrode 202 contains 6 fingers
that are 0.07-mil long, 0.007-mil wide and with a 0.007-mil spacing.

[0046]Referring now to FIG. 6, a circuit diagram of an
impedance-to-frequency converter 404 and electrodes 202 in accordance
with one embodiment of the present invention is shown. A relaxation
oscillator circuitry was selected, which consists of a comparator 600, a
capacitor C1 and several resistors R1, R2, R3, RA and RB. The output
frequency of the oscillator is reversely proportional to the time
constant at the inverting input and can be calculated from the resistance
and capacitance values in the circuit [13]. The electrode 202 is
represented by a variable resistor RS and a variable capacitor CS in
parallel. The material with low impedance such as acid has low resistance
and high capacitance resulting in a high-frequency output. For high
impedance material such as air, the resistance is high and the
capacitance is low resulting in a low-frequency output.

[0047]Now referring to FIG. 7, a circuit diagram of a modulation circuit
700 in accordance with one embodiment of the present invention is shown.
To modulate the data back to the reader, the signal is connected to the
gate of a MOSFET M1, where Vcc is the regulated DC voltage. L1 and C1 are
the transponder antenna 306 and the resonance capacitor 310,
respectively. It is important that the modulation must begin after Vcc
reaches the regulated voltage. This will keep the output of the
impedance-to-frequency converter 404 stable. Moreover, when the
modulation occurs, more energy is required to build up the DC voltage. If
the modulation begins at a low voltage, the read range of the reader 112
will be reduced dramatically.

[0048]To prevent this problem, the transistor M2 is placed at the source
of M1. It will be turned on only when Vcc reaches the regulated value.
The resistors R1 and R2 are added to form a voltage divider converting
the Vcc level to the threshold voltage of M2. When M2 is turned on, M1
behaves as a switch 312 turned on and off by the signals from the
impedance-to-frequency generator 404. When MI is off, L1 and C1 resonate
at the same frequency as that of the reader 112. When M1 is on, the
capacitor C2 is connected to C1 in parallel. This shifts the resonance
frequency of the LC resonant circuit 200 on the transponder 106 resulting
in a variation of signal amplitude at the reader 112.

[0049]Referring now to FIG. 8, an image of a batteryless wireless
impedance sensor 106 prototype in accordance with one embodiment of the
present invention is shown. The prototype was made on a 4-layer printed
circuit board (PCB) with a size of 0.5×1×3 cm3 and
discrete components. If needed, the device size can be further reduced
using smaller surface mounted (SMD) components. A coil antenna 306 of 22
μH was made from a 32AWG magnet wire wound around the PCB. When
connected to a capacitor 310 of 680 pF, the calculated resonant frequency
was 1.3 MHz. The board was then coated with polydimethylsiloxane (PDMS)
to prevent short circuit when placed in the esophagus. A small window
exposes the sensing electrode 202 to make contact with the refluxant.

[0050]Now referring to FIG. 9, a block diagram of a reader or detector 112
in accordance with one embodiment of the present invention is shown. The
detector 112 includes an external resonance circuit 900 formed from an
external coil 304, a power amplifier 902 connected to the external
resonance circuit 900, a radio frequency source 904 connected to the
power amplifier 902, an envelope detector 906 connected to the power
amplifier 902, and a band pass filter 908 connected to the envelope
detector 906. The power amplifier 902 generates high electromagnetic
fields coupling into the transponder 302. The envelope detector 906 reads
the load modulation signals. A frequency source 904 provides carrier
signals feeding to the amplifier 902. The source 904 is adjusted to the
resonant frequency of the LC circuit resulting in a high voltage at the
reader coil 304. When modulation occurs, the voltage level at the reader
coil 304 varies. The signal is extracted by the envelope detector 906 and
fed through a band-pass filter 908 to suppress the high frequency
carrier. Then the frequency-shifted signal is amplified and processed.

[0051]Because biological systems attenuate RF signals at higher carrier
frequencies, carrier frequencies below 10 MHz may be used over distances
of a few centimeters and a carrier frequency of 1.02 MHz was designed for
this example. The external coil 304 may be fabricated on any printed
circuit board (PCB) having consistent mechanical properties regardless of
the dielectric constant selected, and a preferred PCB is the Rogers
RO3003 (Rogers Corp., Chandler, Ariz.). The PCB of one embodiment was
selected with a dielectric constant of 3.0 and a copper thickness of 35
μm and having a PCB thickness of 1.52 mm. For example, a planar
rectangular coil may have 20 turns with a 300-μm width and a 200-μm
spacing and an outer perimeters of 6 cm×6 cm. The calculated
inductance is 38 μH while the measured inductance is 47.32 μH. Any
discrepancy may be due to the undercut etch of the thick copper foil of
the PCB, which can easily reduce the conductor width by 70 μm. A
capacitance of 330 pF was chosen and connected to the coil in series. In
one study, the measured resonance frequency was 1.02 MHz with a quality
factor (Q) of around 7, and in another experience the resonance frequency
was 850 kHz.

[0052]Referring now to FIG. 10, a circuit diagram of a class-E power
amplifier 902 in accordance with one embodiment of the present invention
is shown. The class-E power amplifier 902 was chosen for its high
efficiency. Similar class-E power amplifiers 902 have been considered in
transcutaneous power transfer for many previous works [14-16]. A function
generator 1000 provides 0-5V square wave signals to drive the MOSFET
switch M1. IRL510A was chosen due to its low threshold voltage. A
duty-cycle of 30% was chosen to minimize DC power consumption which would
eventually be provided by batteries in the portable reader. The design
was based on the operating frequency around 1.34 MHz where the
recommended maximum permissible exposure (MPE) of magnetic fields is the
highest in the frequency ranges from 1.34 MHz to 30 MHz [17]. The
operating frequency could be changed according to safety issues,
performance and the allowed frequency bands. A coil antenna 304 with a
size of 12×15 cm2 was made from an AWG26 magnet wire wound around a
frame resulting in an inductance of 17 μH and a high quality Q of 70.
Following the calculation procedures for a high quality factor Q
approximation in [18], the values of C1 and C2 were chosen to be 10 nF
and 900 pF, respectively.

[0053]Now referring to FIG. 11, a circuit diagram of an envelope detector
906 circuit in accordance with one embodiment of the present invention is
shown. The envelope detector 906 includes a diode 1100 and RC networks
1102. The diode 1N4936 (1100) was chosen to rectify the high voltages at
the coil antenna 304 of the class-E amplifier 902. The time constant of
the 100-kΩ resistor and 100-pF capacitor gives a modulation
frequency of 0.1 MHz that is suitable for a carrier frequency above 1
MHz. The 4.7-kΩ resistor and 1-nF capacitor suppress the
high-amplitudes of the high-frequency carrier signals. The 1-nF capacitor
and 100-kΩ resistor form a low-pass filter to reduce the DC level
before the signals are fed to an op-amp buffer 1104. A bandpass filter
908 was made to read the data from the transponder in the 6-12 kHz
bandwidth using op-amps. The signals were then amplified and displayed on
a spectrum analyzer.

[0054]The optimization of read range for inductive coupling RFID has been
discussed in [19].

[0055]Briefly referring back to FIG. 3A, the transponder 302 must receive
sufficient RF powers from the reader 112 in order to operate properly.
The reader 112, on the other hand, must have enough sensitivity to
extract the signals from the transponder 302. The read range thus depends
on the noise level in the environment as well. In general, using higher
electrical currents at the reader 112, using a larger antenna 304 for the
reader 112, making lower power sensor circuitry and/or enlarging the
transponder antenna 306 will enable the system to satisfy power
requirement at a longer distance. Making a high-Q transponder antenna 306
improves the power coupling efficiency but suffers from significant
amplitude drops due to frequency shifts that may be caused by
manufacturing tolerance of components. In a similar manner, although a
high-Q reader antenna 304 improves reader sensitivity, it is also
subjected to noises in the environment increasing the possibility of a
wrong reading. The prototype in this work was optimized for a read range
around 10 cm with reasonable power consumption at the reader. The system
was also tested to be able to read the signals from the transponder 302
in liquid environment.

[0056]Referring now to FIGS. 12A-12D, graphs of detected signals from the
impedance sensor displayed in a spectrum analyzer in accordance with one
embodiment of the present invention are shown. The impedance sensor 106
prototype (FIG. 8) was tested in vitro for characterization. It was
tested in air, water and acid solutions (diluted HCL). The sensor 106
prototype (FIG. 8) was immersed into the solutions in beakers. The reader
antenna 304 was 10 cm away from the sensor 106 and the signals were
monitored with a spectrum analyzer. The DC supply at the reader 112 was
8V and 350 mA. The measurement was also done at a 13-cm distance to
verify the maximum read range. The materials surrounding the electrode
202 were air (FIG. 12A), water (FIG. 12B) and acid (FIG. 12C) with the
reader antenna at a 10-cm distance from the sensor 106. FIG. 12D shows
the detected signals at a 13-cm distance when the electrode 202 was
surround by air. The measured peak frequency was 7.35kHz when the
impedance sensor 106 was in air (FIG. 12A). When the impedance sensor 106
was immersed in water, the peak frequency increased to 8.45 kHz (FIG.
12B). The measured frequency in acid was 11.75 kHz (FIG. 12C) showing
that the acid had very low impedance. The peak frequency was easily
observed with large signal-to-noise ratios at a 10-cm distance between
the sensor and the reader for all test solutions. The frequency shifts
can clearly distinguish air, water and acid solution.

[0057]By shaking the transponder inside the beaker mimicking body motion
artifacts, the signal quality did not change because the impedance
variations were modulated by frequency shifts. The signal attenuation and
fluctuations in the carrier did not degrade the modulated sensor signals
until the regulated DC voltage Vcc in the transponder drops below 2.5V
due to insufficient received energy. The reader 112 was moved farther
away from the transponder 302 to test the read range since the inductive
power coupling decreased proportionally with the cubic power of the
distance [20]. The signal, when measuring the impedance of air, was still
readable at a distance of 13 cm (FIG. 12D), but with more noise.
Accordingly, the system functions well without errors at a read range of
10 cm.

[0058]The prototype of batteryless wireless impedance sensor 106 was
compared with a commercial wireless pH capsule (BRAVO, Medtronic). Both
sensors were bound together using a suture wire. They together were
sequentially immersed in beakers filled with water, orange juice with
pulp (OJ(P)), orange juice without pulp (OJ(N)), carbonated diet cola
drink (Diet Coke®), vinegar and acid solutions. The sensors were
tested again the next day to verify repeatability. After the second day,
the BRAVO capsule ran out of battery and stopped working.

[0059]To validate our sensors, animal study was conducted in the animal
lab at the Southwestern Center for Minimally Invasive Surgery, University
of Texas Southwestern. The experiments were performed on three 6-8 months
old pig cadavers (75 lbs each). Their average chest perimeter was 70 cm
measuring at the level of mid-sternum. The pigs were used in other
surgical studies in which the whole GI tract and the chest were intact.
The pigs were sacrificed immediately before the start of the impedance
sensor experiments. First, an open gastrostomy was created through the
anterior gastric wall in the body of the stomach. The gastroscope
(Olympus GIF 160) was then advanced into the stomach to remove excessive
gastric fluid and content. The sensors were placed in the distal
esophagus about 3 cm proximal to the gastroesophageal (GE) junction under
direct endoscopic guidance. The measurement of the distance was based on
the markings on the shaft of endoscope.

[0060]The reader antenna was attached to the pig's skin outside the body
around chest. With the transponder in the esophagus, we first tested the
motion artifact effects by shaking the pig's body. The sensor signals did
not fluctuate. A 16-French nasogastric (NG) tube was advanced through the
mouth, larynx and into the mid esophagus for flushing various solutions.
The intralumenal location of the NG tube was confirmed by endoscopic
visualization. The NG tube was then secured externally to the skin by
forceps.

[0061]Several solutions were used to test the device performance including
diet cola, orange juice, vinegar, salt solution, acid solution and
alkaline solution (diluted KOH). Water was flushed in between test
solutions to clean the esophagus. A surgical suction tube with continuous
suction was placed inside the stomach to remove excessive solution. After
each flushing of solution through the esophageal tube, intermittent
suction was also applied though the accessory channel of the endoscope to
remove excessive fluids in the distal esophagus right below the implant
sensors.

[0062]The implant location and fluidic activities (solutions of different
colors and clarities) were monitored under direct endoscopic
visualization. Impedance signals were recorded at different time points
corresponding to the flushing of solutions and endoscopic visualization
of solution coming around the implants. The pH sensor (BRAVO device)
results were compared with the readings from our wireless impedance
sensor. The impedance sensor reading was observed immediately since the
frequency shift occurred as soon as the liquid touched the electrode,
while the BRAVO reading delayed until its specific sampling time. The
BRAVO sampling rate is one sample every 30 seconds.

[0063]Now referring to FIG. 13, a graph illustrating the read frequencies
from the impedance sensor in accordance with one embodiment of the
present invention and the respective pH values from the BRAVO device is
shown. The experiments were conducted in beakers. Dash lines indicate the
2nd-day results. Both sensors were tested together twice within 2 days.
After the 2nd day, the battery energy of the BRAVO device was exhausted
and stopped working while the present invention sensor stayed working.
The measured frequencies from the impedance sensor vary between 9 and 11
kHz while the pH values from the BRAVO change from 8 to 2. In general,
the measured frequency shifts are correlated with the pH values. The pH
changes from low to high corresponding to frequency changes from high to
low and vice versa. Orange juice, vinegar, and acid contain significant
amounts of ions and produce low impedances. This results in high
frequency signals from the impedance sensor. The results from the diet
cola, however, were unusual. The diet cola contains carbonic acid with a
low pH value and so it has a low impedance. However, during the
measurements there were bubbles generated from the drink and accumulated
on the electrode. The air bubbles occupied the surface area of the
electrode on the impedance sensor preventing the solution to make a good
electrical contact with the electrode. The measured frequency for the
carbonated cola drink was therefore lower than expected.

[0064]Referring now to FIG. 14, a graph illustrating the measured
frequencies from the impedance sensor in accordance with one embodiment
of the present invention and pH values from the BRAVO device in a pig's
esophagus is shown. The measured frequencies and the pH values were
correlated in the same way as the experiments in beakers. When the acid
solutions such as orange juice, vinegar, and diluted HCL were flushed
into the esophagus, the pH values decreased and the measured frequencies
increased. Between flushing events, the frequency from the impedance
sensor dropped when the liquid left the electrode. However, the frequency
did not go back to the one with air (7.35 kHz) because there was still
some liquid residue left on the electrode. The frequency drop amounts
were also not the same after every flushing due to unpredictable amounts
of residue that might stay on the electrode. The frequency drops however
were sufficiently clear to identify every flushing episode. In the
meantime, the pH values of the BRAVO device remained the same or in the
similar levels. The phenomena of liquid residue left on the electrode
causing incomplete frequency drop back to 7.35 kHz was also observed in
the pH values of BRAVO. After the acidic liquid flushing events, water
flushing was not able to bring the pH values back to 7. This indicates
that there was acidic residue on both the impedance and pH electrodes.

[0065]The arrow and line of the impedance sensor data indicate that the
detected frequency rose from a lower frequency during flushing and
reached the peak frequency in the middle of a flushing event. The peak
frequency stayed the same during flushing. After the flushing finished,
the frequency started to drop. This was observed and verified visually
with the endoscopy. During water flushing for cleaning purpose, the
impedance sensor still indicated each flushing episode as the frequency
increased to local peaks and then decreased while the pH sensor reading
remained the same. As mentioned before, the frequency shifts were
observed immediately when the liquid passed the sensor. The BRAVO pH
sensor readings were recorded with a delay due to the fixed sampling
periods in the device. When more than one flushing events happened within
30 seconds, the BRAVO reading remained the same while the impedance
sensor still detected frequency shifts. In our experiment, each flushing
event was spaced with more than one minute in order to record the BRAVO
data. These results verified that the impedance sensor could detect acid
refluxes and identify every single episode.

[0066]The diet cola event showed the same problem as in the tests done in
beakers. A lot of air bubbles were generated during flushing. The sensor
thus responded to air bubbles as a high impedance air reflux instead of
the carbonic acid in the cola drink. The measured frequency was thus very
low. Nevertheless, the phenomena verify that the device can detect small
air reflux bubbles while the pH sensor cannot.

[0067]Now referring to FIG. 15, a graph illustrating the test results from
the impedance sensor in accordance with one embodiment of the present
invention and pH values from the BRAVO device in another pig cadaver is
shown. The frequency peaks from the impedance sensor were for (a) OJ(N),
(b) OJ(P), (c) vinegar, (d) acid solution, (e) salt solution and (f)
alkaline solution, respectively. Water was flushed between the test
solutions to clean the electrode. The experimental procedure was the same
as before. The data showed that the pH dropped from the base line when
there were acid refluxes caused from orange juice without pulp (OJ(N)),
orange juice with pulp (OJ(P)), vinegar and acid solutions. The measured
frequencies from the impedance sensor increased from the base line
accordingly. The frequency peaks are indicated (a) for OJ(N), (b) for
OJ(P), (c) for vinegar and (d) for acid solutions, respectively. The
impedance and pH sensors showed very high correlation. The results from
the salt solution, however, did not significantly change the pH values
from the BRAVO capsule to indicate reflux episodes because the pH value
of salt solution was close to that of water. The impedance sensor, on the
other hand, detected the salt reflux in the same manner of the acid
reflux as the frequency increased noticeably from the base line (e). For
alkaline reflux, the BRAVO capsule indicated "errors" as the pH was out
of the detection range while the impedance sensor gave high frequency
results indicating the low impedance of the alkaline solution (f).

[0068]The foregoing results demonstrate that an implantable batteryless
wireless impedance sensor for gastroesophageal reflux diagnosis has been
designed, fabricated and validated. The approach is based on impedance
measurement that can detect both acid and non-acid reflux. The wireless
device does not require a battery and so there is no time limit for
monitoring as in other wireless measurement approaches. The device was
tested in pig cadavers demonstrating the feasibility and accuracy of
detecting acid and non-acid reflux episodes. The results showed
comparable performance to the commercial wireless pH sensors (BRAVO) when
detect acid reflux. Furthermore, the impedance sensing method was able to
detect non-acid or alkaline reflux episodes as it could distinguish air
from water, acid and alkaline solutions. The read range was demonstrated
with the reader at a 10-cm distance from the transponder in a beaker and
through the pigs' body with an average chest perimeter of 70 cm. The
signals were clear without interference of motion artifacts. The
transponder prototype was small enough for use in esophagus even it was
built with discrete components. Eventually the transponder can be
designed with an integrated chip to further reduce implant sizes as those
used in RFID tags. The custom designed chip will enable ultra low power
consumption and be capable of much longer read ranges.

[0069]Other embodiments and design considerations will now be described.
For example, FIGS. 16A, 16B and 16C illustrate various antenna
configurations in accordance with the present invention. FIG. 16A shows a
sensor configured as a capsule 1600 attached to esophagus wall 1602
wherein the antenna is formed by a coil 1604 wrapped lengthwise around a
ferrite coil 1606. FIG. 16B shows a sensor configured as a capsule 1610
attached to esophagus wall 1602 wherein the antenna is formed by a coil
1612 wrapped widthwise around a ferrite coil 1606. FIG. 16c (side and
front views) shows a sensor configured as a tag 1620 attached to
esophagus wall 1602 wherein the antenna is formed by a planar coil 1622
disposed on a flexible substrate that is wrapped along the perimeter of
the tag 1620.

[0070]FIGS. 17A and 17B illustrate various packaging configurations in
accordance with the present invention. FIG. 17A shows a sensor configured
as a capsule 1700 having an impedance sensing electrode 202 and a passive
batteryless RFID circuit 204 on a chip connected by wire 1702. The LC
resonance circuit 200 includes a coil 1704 wound widthwise around a
ferrite core 1706 and connected to the passive batteryless RFID circuit
204 by wire 1708. The capsule 1700 also includes space 1710 for
attachment to the esophagus wall. FIG. 17B shows a sensor configured as a
tag 1750 having an impedance sensing electrode 202 and a passive
batteryless RFID circuit 204 on a chip connected by planar circuitry
1752. The LC resonance circuit 200 includes a planar coil 1754 disposed
on a flexible or non-flexible substrate that is wrapped along the
perimeter of the tag 1750 and connected to the passive batteryless RFID
circuit 204 by wire 1756. The capsule 1700 also includes space 1758 for
attachment to the esophagus wall.

[0071]FIGS. 18A and 18B illustrate various array configurations in
accordance with the present invention. FIG. 18A shows an array implant
configuration 1800 wherein five sensors 1802a, 1802b, 1802c, 1802d and
1802e are attached to, partially encapsulated by, or connected by a
biodegradable substrate 1804 that attaches to the esophagus wall at point
1806. The substrate 1804 degrades and breaks apart after approximately 48
hours. The sensors 1802 then pass through the GI tract and are expelled.
Each sensor 1802 is on a flexible substrate, has its own resonant
frequency and its own RFID to identify location. FIG. 18B shows an array
implant configuration 1850 wherein a capsule 1852 is connected to four
sensor electrodes 1854a, 1854b, 1854c and 1854d that are attached to,
partially encapsulated by, or connected by a biodegradable substrate 1804
that attaches to the esophagus wall at point 1806. The substrate 1804
degrades and breaks apart after approximately 48 hours. The sensors
electrodes 1854 then pass through the GI tract and are expelled. The
metal also breaks apart and is expelled.

[0072]FIG. 19 illustrates a system having multiple wireless impedance
sensors in accordance with the present invention. This embodiment of the
present invention uses passive telemetry to wirelessly monitor reflux 102
from an animal's stomach 104 using a multiple small passive sensors 106a,
106b, 106c and 106d without a battery that can be attached to the
esophagus 108 wall. The implanted sensors 106a-d harvest radio frequency
(RF) powers 110 transmitted from an external reader or detector 112 and
transduces impedance variations in the esophagus 108 as RF signals back
to the reader 112.

[0073]As shown in FIGS. 20A-20F, the coil and the electrodes may be
fabricated by a photolithography processes 2000. First, a 2000-Å seed
layer 2002 of Cu was thermally evaporated onto a flexible polyimide
substrate 2004, such as Kapton® film (DuPont, Wilmington Del.)
although any similar flexible substrate is acceptable FIG. 20A.
Photoresist 2006 (such as NR7-3000P obtained from Futurex or any suitable
photoresist) was spin coated, baked and patterned for the coil and the
electrodes mold FIG. 20B. A seed layer of Cr/Cu/Cr or Ti/Cu/Ti can be
used for better adhesion of Kapton/Cu and Cu/photoresist interfaces (not
shown). The thick photoresist layer was achieved by two layers of
NR7-3000P with a spinning speed of 1000 rpm for 30 seconds. The baking
temperatures and times of the 1st and 2nd layers are
120° C./1 min and 150° C./1 min 20 sec, respectively. The
sample was exposed to UV light and baked at 120° C. for 70 sec.
The baking was done in an oven to evenly heat the photoresist on the
non-flat substrate. The sample was put in a Cu electroplating solution
for 2 hours with an electrical current of 10 mA. A total Cu layer of
about 8 μm was formed, FIG. 20C, to achieve low resistance. The
photoresist was removed by putting the sample in an ultrasonic bath with
acetone for 10 min and then the Cu layer was etched away, as shown in
FIG. 20D. A 10-μm thick layer 2008 of an epoxy-based negative resist
(such as SU-8 made by MicroChem, Newton, Mass. however any similar
epoxy-based negative resist is suitable) was spun, patterned and then
hard cured onto the coil area to prevent undesired electrical contact, as
shown in FIG. 20E. The sample was then Ni electroplated 2010 to protect
the Cu electrode from corrosion in acid, as shown in FIG. 20F. FIG. 21
shows an electrode 202 having interdigitated fingers that are about 0.4
mm wide and about 5 mm long with about 0.1 mm spacing there between. The
sensitivity of the sensor can be adjusted by changing the width, length
and spacing of the interdigitated fingers of the electrode.

[0074]FIG. 22 shows a connector (jumper wire) used to complete the circuit
of the coil and the electrodes. This also can be done by depositing a
metal airbridge with first thermal evaporator and then electroplating
processes. The coil inductance was measured as 9.41 μH, which is close
to the theoretical value of 9.1 μH. The measured DC resistance of the
coil is 13 Ω resulting in a calculated quality factor (Q) of 4.63
using the equation Q=ωL/R, where ω is the angular frequency.
The Q value can be improved by plating a thicker Cu layer to reduce the
coil resistance. The capacitance for the resonance frequency at 1.02 MHz
was calculated to be 2587 pF. An SMD (surface mount device) capacitor of
2200 pF, the closest value available, was selected and soldered onto the
sample. A metal-insulator-metal (MIM) capacitor can be fabricated instead
to achieve the exact capacitance in the future without using the hybrid
components. Interdigitated electrodes are located in the center of planar
coil so that it is in the outer area to maximize the inductance.

[0075]To further characterize the preferred structure of the electrode(s)
of the impedance sensor in measuring acid refluxate, three electrodes
were fabricated to investigate the performance of the interdigitated
structures. Each design has the total area of 1×1 cm2 with
different finger widths and spacings. The capacitances of the electrodes
when immersed in air, city water and simulated stomach acid (70:1 and
50:1 muriatic acid) were measured and are shown in Table 1.

[0076]Referring to Table 1 (above), the capacitance of the electrodes in
air is much lower than in water or acid. The capacitance in acid reaches
the μF ranges for all designs, which is much higher than those in air
or water. The results show that smaller finger spacing and narrower
finger width (which means more fingers) result in higher capacitance for
electrodes with the same total area. The dimensions of the electrodes can
be adjusted with the parameters in mind to achieve a desired sensitivity
for specific impedance measurements.

[0077]Additional information regarding the use of FSK modulation will now
be described. The device operating with direct modulation (or amplitude
modulation) is susceptible to noise, and the relative accuracy will vary
with the distance between the tag and reader due to different body types
and the body movement of the patient. To mitigate the possibility of
noise affecting the impedance signal, frequency shift keying may
optionally be used. Frequency Shift Keying (FSK). Frequency shift keying
(FSK) provides very high noise immunity. K. Finkenzeller, RFID Handbook:
Fundamentals And Applications In Contactless Smart Cards And
Identification, Chichester, England, New York: Wiley, 2003, and Y. Lee
and P. Sorrells, "Passive RFID basics," Application Note AN680, Microchip
Technology Inc., relevant portions incorporated herein by reference. The
FSK signal is less susceptible to the misalignment in coupling coils and
artifacts from motion, which are two major problems in biomedical
implants.

[0078]A FSK system has two operating frequencies that are digitally
generated by a series of D flip-flops to divide the carrier frequency
from the reader. D. Liu, X. Zou, Q. Yang and T. Xiong, "An analog
front-end circuit for ISO/IEC 15693-compatible RFID transponder IC,"
Journal of Zhejiang University-Science A, Vol. 7, No. 10 pp. 765-1771,
2006, herein incorporated by reference. In the present invention, the
transmitted impedance signal is analog, which needs to be transmitted
instead of the `0` and `1` bits of the FSK signal. The signal is related
to the impedance of esophagus measured by the electrodes. The frequency
thus needs to vary between f1 and f2 to reflect the impedance ranging
between air and acid. To create FSK signals, astable multivibrator
circuits are used with the present invention to reduce signal noise,
S.-M. Wu, J.-R. Yang and T.-Y. Liu, "An ASIC for transponder for radio
frequency identification system," Proceedings of the Ninth Annual IEEE
International ASIC Conference and Exhibit, pp. 111-114, (1996), herein
incorporated by reference. The generated frequency is directly related to
a variable capacitor in the circuits, which in the present invention, is
the impedance electrodes of the tag.

[0079]To verify the feasibility, a study was conducted using a modified
commercial timer IC TS555 (STMicroelectronics, Carrollton, Tex.) or any
suitable time IC in the astable mode operating at 1.5V, where the
capacitor, C, in the connection diagram was replaced by the sensing
electrodes of the tag. Table 2 (below) shows the capacitance of
electrodes with a finger size of 250 μm wide and 50 μm spacing.

[0080]The frequency of the square wave generated by TS555 can be
calculated from the equation:

f = 1.44 ( R A + 2 R B ) C

The capacitance of the sensing electrodes 44, however, can vary from pF to
μF in air and acid, which can make the TS555 IC timer unable to
operate in the whole range of the frequency, and moreover, the systems
will require very high bandwidth, which is difficult to achieve at both
the tag and reader. To keep the capacitance in the desired range, two
fixed capacitors C1 and C2 were added.

[0081]The series and parallel connection with the additional capacitors
keeps the total capacitance in the range of C1 (62) and C2 (64) where
C2>>C1. When there was only air on the electrodes, the impedance
was high and the total capacitance is close to lnF resulting in an output
frequency of 263 kHz. When acid was dropped onto the electrode, the total
capacitance reached 11 nF. Considering the sensing electrodes also
measure resistance, the output frequency still varies with respect to the
capacitance change. The frequency reduced to 68.5 kHz and 40.5 kHz when
water and simulated stomach acid were on the electrodes, respectively.

[0082]The integrated RFID chip can be connected to the electrodes and the
resonance capacitor by wire bonding. The flip-chip bonding used for
conventional RFID tags is suitable for this configuration to reduce
parasitics and costs. The tag's antenna, capacitor and the electrode can
be fabricated together in a batch fashion using standard photolithography
as previously described. The astable multivibrator circuits can be
designed together with a traditional RFID circuitry and sensor/ID
control. The frequency generated from the astable multivibrator can be
used to trigger a transistor connected to the LC resonance circuit on the
tag. The sensor modulator includes astable mutivibrator circuits
connected to sensing electrodes. The modulator turns the transistor on
and off with the frequency corresponding to the measured impedance. This
transistor tunes and detunes the LC resonance circuit and creates signal
envelope variation at the reader. The impedance value can be extracted by
counting the number of high frequency carrier pulses between the edges of
the signal envelopes.

[0083]As with an individual tag, FSK is also helpful in the array
(multiple tag) aspect of the present invention. In the array, a reader
reads a first impedance sensor then reads the FSK to determine if there
is refluxate in the vicinity of the first sensor. Then the reader or an
additional reader interrogates a second impedance sensor and reads FSK to
determine if there is refluxate in the vicinity of the second sensor and
so on. This array configuration permits a user to predict the flow of the
refluxate and take preventative measures before the problem is
exacerbated, for instance, before refluxate reaches to the top of the
esophagus. In this aspect, the reader (external resonance circuit) may be
uniquely coupled to one tag (impedance sensor) or may read a subset of
tags, or the entire set of tags.

[0084]At the reader, the square waves will be extracted, and the frequency
will be calculated from the number of pulses in a certain amount of time,
or the sampling period. In practice, the impedance monitoring can be done
at 50 samples per second or 20 ms sampling period. In 20 ms, at least 2
pulses must be transmitted from the tag for the correct frequency
calculation at the reader. The reading frequency is the number of pulses
divided by the sampling period which is the average frequency transmitted
from the tag. The minimum frequency requirement of the FSK modulation is
thus around 100 Hz. A higher frequency can increase the sampling rate and
is less subjected to the distortion from carrier rejection filter which
is used in most demodulation circuit at the reader.

[0085]The carrier frequencies have a wide range between 100 kHz and 1 MHz
depending on practical considerations. A lower frequency has better
penetration through human tissues, however, its shorter propagation range
is the tradeoff. The frequency of 125 kHz ISM band is suitable for the
FSK our applications since the propagation distance is short. The
modulation frequency around fc/8 or fc/10 will allow the
sampling rate of several kilohertz, which is more than enough for
impedance monitoring.

[0086]FIG. 23 shows a sensor disposed on a flexible substrate in
accordance with one embodiment of the present invention. FIG. 24 shows a
sensor configured for use in a tag in accordance with one embodiment of
the present invention. Additional information and test results can be
found the provisional patent application identified above and in the
inventor's previously published articles and papers listed below as
References [12,30,36,37], which are hereby incorporated by reference in
their entirety.

[0087]It is contemplated that any embodiment discussed in this
specification can be implemented with respect to any apparatus, method,
kit or system of the invention, and vice versa. Furthermore, compositions
of the invention can be used to achieve methods of the invention. It will
be understood that particular embodiments described herein are shown by
way of illustration and not as limitations of the invention.

[0088]The principal features of this invention can be employed in various
embodiments without departing from the scope of the invention. Those
skilled in the art will recognize, or be able to ascertain using no more
than routine experimentation, numerous equivalents to the specific
procedures described herein. Such equivalents are considered to be within
the scope of this invention and are covered by the following claims.

[0089]All publications and patent applications mentioned in the
specification are indicative of the level of skill of those skilled in
the art to which this invention pertains. All publications and patent
applications are herein incorporated by reference to the same extent as
if each individual publication or patent application was specifically and
individually indicated to be incorporated by reference.

[0090]The use of the word "a" or "an" when used in conjunction with the
term "comprising" in the claims and/or the specification may mean "one,"
but it is also consistent with the meaning of "one or more," "at least
one," and "one or more than one." The use of the term "or" in the claims
is used to mean "and/or" unless explicitly indicated to refer to
alternatives only or the alternatives are mutually exclusive, although
the disclosure supports a definition that refers to only alternatives and
"and/or." Throughout this application, the term "about" is used to
indicate that a value includes the inherent variation of error for the
device, the method being employed to determine the value, or the
variation that exists among the study subjects.

[0091]As used in this specification and claim(s), the words "comprising"
(and any form of comprising, such as "comprise" and "comprises"),
"having" (and any form of having, such as "have" and "has"), "including"
(and any form of including, such as "includes" and "include") or
"containing" (and any form of containing, such as "contains" and
"contain") are inclusive or open-ended and do not exclude additional,
unrecited elements or method steps.

[0130]It will be understood by those of skill in the art that information
and signals may be represented using any of a variety of different
technologies and techniques (e.g., data, instructions, commands,
information, signals, bits, symbols, and chips may be represented by
voltages, currents, electromagnetic waves, magnetic fields or particles,
optical fields or particles, or any combination thereof). Likewise, the
various illustrative logical blocks, modules, circuits, and algorithm
steps described herein may be implemented as electronic hardware,
computer software, or combinations of both, depending on the application
and functionality. Moreover, the various logical blocks, modules, and
circuits described herein may be implemented or performed with a general
purpose processor (e.g., microprocessor, conventional processor,
controller, microcontroller, state machine or combination of computing
devices), a digital signal processor ("DSP"), an application specific
integrated circuit ("ASIC"), a field programmable gate array ("FPGA") or
other programmable logic device, discrete gate or transistor logic,
discrete hardware components, or any combination thereof designed to
perform the functions described herein. Similarly, steps of a method or
process described herein may be embodied directly in hardware, in a
software module executed by a processor, or in a combination of the two.
A software module may reside in RAM memory, flash memory, ROM memory,
EPROM memory, EEPROM memory, registers, hard disk, a removable disk, a
CD-ROM, or any other form of storage medium known in the art. Although
preferred embodiments of the present invention have been described in
detail, it will be understood by those skilled in the art that various
modifications can be made therein without departing from the spirit and
scope of the invention as set forth in the appended claims.

Patent applications by Jung-Chih Chiao, Grand Prairie, TX US

Patent applications by Thermpon Ativanichayaphong, Valencia, CA US

Patent applications by Board of Regents, The University of Texas System